Genetic Markers Associated to Dyslipidemia in HIV‐Infected Individuals on HAART

Abstract

This study evaluated the impact of 9 single nucleotide polymorphisms (SNPs) in 6 candidate genes (APOB, APOA5, APOE, APOC3, SCAP, and LDLR) over dyslipidemia in HIV-infected patients on stable antiretroviral therapy (ART) with undetectable viral loads. Blood samples were collected from 614 patients at reference services in the cities of Porto Alegre, Pelotas, and Rio Grande in Brazil. The SNPs were genotyped by conventional polymerase chain reaction (PCR) and real-time PCR. The prevalence of dyslipidemia was particularly high among the protease inhibitors-treated patients (79%). APOE (rs429358 and rs7412) genotypes and APOA5 −1131T>C (rs662799) were associated with plasma triglycerides (TG) and low-density-lipoprotein cholesterol levels (LDL-C). The APOA5 −1131T>C (rs662799) and SCAP 2386A>G (rs12487736) polymorphisms were significantly associated with high-density-lipoprotein cholesterol levels. The mean values of the total cholesterol and LDL-C levels were associated with both the APOB SP Ins/Del (rs17240441) and APOB XbaI (rs693) polymorphisms. In conclusion, our data support the importance of genetic factors in the determination of lipid levels in HIV-infected individuals. Due to the relatively high number of carriers of these risk variants, studies to verify treatment implications of genotyping before HAART initiation may be advisable to guide the selection of an appropriate antiretroviral therapy regimen.

Association of single nucleotide polymorphisms with dyslipidemia in antiretroviral exposed HIV patients in a Ghanaian population: A case-control study

“…Such reported side effects are not universal to all individuals on ART and may even vary in individuals with comparable ART, demographic, immunologic and virological characteristics [12][13][14]. This variability suggests that genetic factors and inherited predispositions may have a significant influence on the incidence of metabolic dysfunction [14,15]. However, high HDL cholesterol and apolipoprotein A-I (APOA-I) have been directly associated with a better immunological outcome [16].…”

“…Moreover, HIV-infected patients who harbor polymorphisms of the DSCAML1 (Down syndrome cell adhesion molecule like-1) gene exhibit a less favorable lipids profile [23,24]. Current studies have suggested the relationship between the level of lipids and LDLR, ABCA1 APOA5, and DSCAML1 polymorphisms [15,25].…”

“…Nevertheless, the exact mechanism of dyslipidemia is not fully understood but is most likely multifactorial with the genetic variation being shown to account for about 43-83% of the variability of plasma lipoprotein levels in a normal healthy population [16,26]. Therefore, from the genetic perspective, HAART-associated hyperlipidemia could be under the influence of various forms of genetic polymorphisms, similar to that in non-HIV adults [27,28]. Several single nucleotide polymorphisms (SNPs) that could account for a significant portion of the variation of blood lipoprotein concentrations have been identified through recent candidate gene studies and genome-wide association studies (GWAS) [15,29].…”

Síndrome lipodistrófica do HIV e seus fatores associados: um estudo em um hospital universitário

“…We found no association between HIV-associated lipodystrophy and dyslipidemia or altered fasting glucose. However, previous studies have reported these associations [67][68][69] . In a cross-sectional study conducted in Thailand with 278 patients infected by HIV, 93% of those with lipodystrophy had at least one metabolic abnormality (dyslipidemia, glucose intolerance or insulin resistance) 70 .…”

HIV-associated lipodystrophy: a review from a Brazilian perspective

“…Several mechanisms, including molecular homology between HIV protease and some proteins involved in lipid metabolism and inhibition of plasmatic lipoprotein lipase, have been described 11,23. Genetic predisposition could explain, at least in part, the large heterogeneity between patients in relation to the intensity of the effects of PIs on lipid metabolism 24. Elevations in total cholesterol can also occur with d4T, ZDV, and efavirenz 25…”